儿童EB病毒相关性噬血细胞淋巴组织细胞增生症的临床特征和预后危险因素分析  

Clinical analysis and follow-up study of Epstein-Barr virus associated-hemophagocytic lymphohistiocytosis in childhood

作　　者：卢根[1] 谢正德[2] 申昆玲[1] 吴润晖[3] 金颖康[1] 杨双[3] 刘春艳[2] 

机构地区：[1]首都医科大学附属北京儿童医院内科,100045 [2]首都儿科研究所病毒室 [3]首都医科大学附属北京儿童医院血液中心,100045

出　　处：《中华儿科杂志》2010年第2期121-126,共6页Chinese Journal of Pediatrics

基　　金：首都医学发展科研基金项目（2007-2062）

摘　　要：目的分析儿奄EB病毒相关性噬血细胞淋巴组织细胞增生症（EBV—HLH）的临床特征，探讨影响其预后的危险因素。方法采用回顾性调查方法，对2003年5月至2008年9月收治的62例EBV—HLH患儿临床特征、血清学、病毒载量、病理改变、基因筛查及预后资料进行系统分析。根据随访的生存情况分为生存组和死亡组，采用单因素和多因素Logistic回归分析影响预后的危险因素。结果（1）62例患儿中，男36例，女26例，发病年龄2个月～14岁，26例（41．9％）在婴幼儿期发病，38例（61．3％）发病是由于EBV感染再激活所致；（2）所有患儿均有持续或间断发热，至少有外周血两系减低。伴有肝肿大52例，脾肿大45例，淋巴结病43例。58例患儿血清白蛋白降低，52例血清铁蛋白增高，大部分患儿伴有凝血功能异常和脂质代谢紊乱。48例诊断时骨髓中出现吞噬血细胞现象；31例EBV—HLH患儿中14例血清中EBV—DNA检测阳性，病毒载量拷贝数在5．12×10^2～7．69×10^7／ml之间（平均10^3.9／ml）；（3）在3例EBV—HLH的PRF1基因外显子编码区发现3个杂合错义突变，这3个突变均导致氨基酸改变（C102F，S108N和T450M），1例患儿为复合杂合错义突变（S108N和T450M），从遗传学上可明确诊断为家族性噬血细胞淋巴组织细胞增生症亚型2（FHL2）；（4）随访57例病例中35例（61．4％）死亡，其中21例经过HLH-94或04治疗方案。15例是在住院后2个月内死亡。死亡病例相比存活病例白蛋白降低和部分凝血激酶时间延长（P均〈0．05）。多因素Logistic回归分析显示病程大于1个月、未进行免疫化疗、白蛋白≤25g／L和深部出血与EBV—HLH的预后呈显著相关性（P均〈0．05）。结论EBV—HLH患儿病情严重，预后凶险，病死率高；多数病例由于EBV感染再激活所致；早期诊断并尽早开始化疗可以提高患儿的存活率；病程�Objective To identify the clinical characteristics of and to explore the prognostic factors influencing mortality in children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis （EBV-HLH）. Method A retrospective study was conducted on 62 pediatric patients with EBV-HLH who were admitted to our hospital between 2003 and 2008. All their medical records were reviewed and analyzed. For each patient, demographic, clinical and laboratory data, genetic findings and outcome information were collected. The patients were divided into two groups： deceased or survived based on the follow-up results. Comparative analysis of the data was done by using independent-samples t test and Logistic multiple and univariate regression. Result （ 1 ） Among the 62 EBV-HLH patients, 36 were male and 26 were female. The age of onset ranged from 2 months to 14 years and most of the patients were between 1 and 3 years of age. EBV-HLH occurred mainly in the setting of reactivation （61.3%）. （2） All patients exhibited persistent or intermittent fever and cytopenia ≥ 2 cell lines. Most of the patients presented with hepatomegaly （83.9%）, splenomegaly （72. 6% ） and lymphadenopathy （69. 4% ）. The main laboratory features showed an elevation of serum ferritin and aminotransferase levels. A reduction in serum albumin was observed and exhibited coagulopathy with hypofibrinogenemia and hypertriglyceridemia in most of the patients. Forty-eight of patients had hemophagocytosis in bone marrow at diagnosis of EBV-HLH. The serum EBV DNA level in 14 of 31 patients with EBV-HLH was in the range of 5.12 × 10^2 -7. 69 × 10^7 copies/ml with a mean value of 10^3.9 eopies/ml. （3） Three heterozygous mutations in coding region were found, which resulted in amino acid change （C102F, S108N and T450M） in 3 patients. One patient had compound heterozygous mutations （S108N and T450M） in the PRF1 gene as the background defect and documented familial HLH type 2 （FHL2）. （4） During the observational period

关 键 词：疱疹病毒4型 人 淋巴组织细胞增多症 嗜血细胞 儿童 危险因素 

分 类 号：R72[医药卫生—儿科]